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Purpose To present a case of endophthalmitis caused by Abiotrophia defectiva after repeated injections of dexamethasone intravitreal implant (Ozurdex), in a patient already on systemic immunosuppressive therapy, and discuss the management of this challenging situation. Methods Case report and review of literature. Results A 70-year-old female patient with history of idiopathic pulmonary fibrosis presented for urgent evaluation due to left eye vision loss and mild discomfort 12 days after receiving her seventh dexamethasone implant injection. Ocular history was pertinent for recurrent macular edema resulting from a remote branch vein occlusion. Twelve days after her last injection, visual acuity decreased from 20/30 to counting fingers at 5 feet. Slit-lamp examination showed anterior chamber cell without fibrinoid membranes or hypopyon. Within hours, the patient's clinical appearance progressed. A vitreous tap followed by intravitreal injection of vancomycin (1 mg/0.1 mL) and ceftazidime (2.25 mg/0.1 mL) was performed. The culture from the vitreous sample revealed heavy growth of A. defectiva. Owing to limited improvement, patient was taken to the operating room, and the presence of a full-thickness scleral defect at the site of most recent dexamethasone implant injection was confirmed. Vitrectomy with removal of implant, closure of all sclerotomies, including nonhealing full-thickness scleral defect, and repeated intravitreal antibiotic injection were performed. At the 3-month follow-up, no inflammation was observed, but visual acuity remained poor. Conclusion Intravitreal dexamethasone implant-associated endophthalmitis in the setting of systemic immunosuppression is a rare and challenging situation. Both local and systemic immunosuppression may delay wound healing, predisposing to wound leakage and consequent endophthalmitis. Despite repeated intravitreal antimicrobial injection and vitrectomy with implant removal, A. defectiva endophthalmitis carried a poor visual outcome.

Patients with chronic spinal cord injury suffer from a number of pathophysiological alterations that can lead to im-portant morbidity and mortality in the perioperative period. The diaphragmatic pacemaker is a device that enables pulmonary ventilation in patients with high cervical cord injuries and provides them with a better quality of life when compared to mechanical ventilation. We present here the clinical case of a patient with chronic spinal cord injury who used a diaphragmatic pacemaker, and who was scheduled for percutaneous nephrolithotomy and double-J stent implantation. The anesthesiologist should know the pathophysiological situation of these patients in order to provide a safe perioperatory care.

Objective Clopidogrel is a commonly used antiplatelet agent for the prevention of thromboembolic complications following neuroendovascular procedures, but anecdotal data have raised concern for the possibility that clopidogrel may induce severe, intolerable fatigue. The purpose of this study is to systematically investigate this phenomenon. Methods We performed a dual-institution, 9-year, retrospective study of patients undergoing clopidogrel therapy for neuroendovascular procedures. Patients were included only if their response to clopidogrel was assessed by platelet function testing using the VerifyNow P2Y12 (VNP) assay. Hyperresponse to clopidogrel was defined as P2Y12 reaction units ≤60. Patients were considered to have had clopidogrel-induced severe fatigue if the onset of symptoms followed the initiation of clopidogrel therapy; symptoms improved following a reduction in the dose of clopidogrel; and symptoms could not be attributed to any other medical explanation. Results Data were collected on 349 patients. Five patients (1.4%) met criteria for clopidogrel-induced severe fatigue. All 5 patients were female, ages 39–68. VNP assessments obtained while patients were symptomatic revealed hyperresponse to clopidogrel (0–22 P2Y12 reaction units). Symptoms improved in all 5 patients when the dose of clopidogrel was reduced by half. Notably, 30% of patients (n = 103) demonstrated a hyperresponse to clopidogrel on at least 1 VNP assessment, but 98 of these patients did not suffer from severe fatigue. Conclusions A syndrome of severe fatigue and other constitutional symptoms is a rare but clinically significant side effect of hyperresponse to clopidogrel in patients undergoing neuroendovasular intervention.

PURPOSE To present the first case of acute macular edema with serous retinal detachment after cataract surgery in a vitrectomized eye. METHODS A 63-year-old female patient, with history of pars plana vitrectomy and epiretinal membrane removal, underwent uneventful phacoemulsification surgery with injection of standard intracameral dose of cefuroxime (1 mg/0.1 mL of solution) at the end of the procedure. RESULTS First day after cataract surgery, visual acuity did not correlate with anterior segment findings, and funduscopic eye examination revealed acute macular edema with serous retinal detachment, which was confirmed by spectral domain optical coherence tomography. Fluorescein angiography showed no retinal or choroidal hyperpermeability. At 2-week follow-up visit, visual acuity had significantly improved, and there was complete resolution of macular edema and subretinal fluid. CONCLUSION The current case suggests that acute macular edema with serous retinal detachment after cataract surgery with standard cefuroxime prophylaxis can occur even in vitrectomized eyes. A high level of suspicious is needed when visual acuity does not correlate with anterior segment findings immediately after cataract surgery. Similar to reports from nonvitrectomized eyes, visual prognosis was favorable.

Objective Post-traumatic stress disorder (PTSD) can develop after a life-threatening medical event. According to the enduring somatic treat (EST) model, internal somatic cues (e.g., rapid heart rate) may contribute to symptoms of stroke/TIA-induced PTSD. To address this possibility, the present study tested the association of stroke-induced disability with PTSD symptoms in patients treated for stroke or transient ischemic attack (TIA). Method Participants (n = 300) were drawn from an observational cohort study examining PTSD symptoms in patients admitted to the NewYork Presbyterian Hospital between 2015 and 2017 for a stroke/TIA. Patients self-reported acute stress symptoms in-person approximately 3 days post-stroke/TIA and PTSD symptoms via telephone one month later. Severity of stroke symptoms (i.e., stroke disability) was evaluated using the NIH Stroke Scale prior to hospital discharge. Results Stroke disability had a significant, positive association with acute stress symptoms early post-stroke/TIA, B = 0.46, se = 0.15, p = .002, and with PTSD symptoms one month later, B = 0.56, se = 0.19, p = .003. Conclusions Stroke disability is positively associated with both acute distress and PTSD symptoms one month later following a stroke/TIA, supporting the hypothesis that internal somatic symptoms contribute to the development stroke/TIA-induced PTSD symptoms.

Las enfermedades musculares estaban infrarrepresentadas en los libros de texto hasta hace pocas décadas, sin considerar la importancia de la masa y las funciones de los músculos esqueléticos y sus cambios relacionados con el envejecimiento. En 1987 se creó el término sarcopenia para definir la pérdida de masa y función del músculo esquelético y sus importantes consecuencias funcionales. Desde entonces su definición ha progresado con los avances de la investigación. En este artículo se revisan los primeros pasos de esta enfermedad, inicialmente definida solamente por la baja masa muscular, mediante la incorporación progresiva de la función muscular y el rendimiento físico. Se describe luego la aparición de varias definiciones de consenso de sarcopenia alrededor de 2010. Estas definiciones demostraron que la sarcopenia aumenta de forma muy significativa la mortalidad, las caídas y la dependencia funcional. Aunque permitieron que la sarcopenia fuera incluida en la clasificación internacional de enfermedades, no lograron que fuera diagnosticada de forma habitual en la práctica clínica. Se revisan por último las actualizaciones de estas definiciones en los últimos dos años, con la intención de que su traslación a la práctica permita empezar a aliviar las graves consecuencias de la sarcopenia.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.

Background oropharyngeal dysphagia (OD) and hip fracture are common problems in older patients, both associated with important complications. Objective the aim of this study was to measure the prevalence and identify the main risk factors of dysphagia in older patients with hip fracture. Design a prospective study in an orthogeriatric unit of a university hospital over 10 months. Methods a total of 320 patients (mean age 86.2 years, 73.4% women) were assessed for dysphagia within 72 hours post-surgery using the Volume-Viscosity Swallow Test. Geriatric assessment, hip fracture management and complications were examined to determine their relationship with the presence of OD. Results dysphagia was present in 176 (55%) patients. Multivariate logistic regression analysis showed that the presence of delirium during hospitalization and the inability to perform instrumental activities of daily living before admission were associated with OD. Conclusions the prevalence of OD is high in hip fracture patients. Objective dysphagia assessment should be routinely included as part of the geriatric assessment of such patients.

We aimed to evaluate and compare the Short Form of the Mini Nutritional Assessment (MNA-SF) as a nutritional screening tool with the new Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition (the most current reference standard) among older patients with cancer. Patients ≥ 70 years old, with a G8 screening tool ≤ 14, referred to an oncogeriatric clinic. MNA-SF and GLIM criteria were obtained. 40 patients were included (mean age 84.8 ± 5.5, 60% male). According to the GLIM diagnostic criteria, 57.5% were malnourished. The MNA-SF classified 80% as being malnourished or at risk of malnutrition. MNA-SF showed a high sensitivity (100%) and a low specificity (50%) to detect GLIM-defined malnutrition. The AUC of the ROC curve was 0.75. The MNA-SF scale is useful as a screening tool to detect malnutrition in older cancer outpatients.

Background Historically, adults with ultra short bowel syndrome (USBS) have been considered candidates for lifetime parenteral nutrition (PN) or are referred for visceral transplantation. We examined the surgical and nutritional outcomes of adult patients with USBS managed at a single intestinal rehabilitation center. Methods We retrospectively reviewed data on 588 adult patients referred to our center between January 2013 and December 2018. USBS was defined as residual small bowel (SB) length ≤ 50 cm. Results Forty-five patients (7.6%) with a mean age of 46.7 years (range 17-78) were identified. Indications for enterectomy included mesenteric ischemia (n=17) and internal hernias (n=6), followed by large intraabdominal fibroids, trauma, and allograft enterectomies, with five cases each. Median SB length was 18.0 cm; 20 patients (44.4%) had their entire SB resected. Thirteen patients had an intact colon, of which nine had preservation of the ileocecal valve. Patients who underwent autologous reconstruction of their gastrointestinal (GI) tract required a lower total PN volume (29.0 ± 7.6 vs. 40.8 ± 13.2 ml/Kg/day, p=0.002) and presented better short- and long- term survival (p=0.005). Patients with no gut had higher mortality (p=0.036). Hormonal therapy with the glucagon-like peptide-2 analog teduglutide was used in nine patients (20%) five of whom were weaned off TPN. Excluding patients with no gut (n=20), discontinuation of total PN rate for patients with an end ostomy or tube decompression (n= 6), jejunocolostomy (n= 10), and jejunoileostomy (n=9) were 0%, 40%, and 77.7%, respectively. Eleven patients (44%) with some residual small intestine achieved nutritional autonomy in an average of 20 months after GI reconstruction. Fifteen patients were listed for transplantation (33.3%). Seven patients underwent isolated SB transplantation and achieved nutritional autonomy in an average of three months after transplantation. One-year patient and graft survival were 100%. After a 37-month median follow-up period, 36 of 42 patients followed by our center were still alive (85.7%). Conclusion Nutritional autonomy can be achieved in a significant number of patients with USBS in specialized centers with surgical and/or hormonal therapy. The presence of an intact colon and ileocecal valve can significantly increase the adaptation rate. Moreover, restoration of GI tract continuity has a positive impact on medical management and survival.

Experimental and computational techniques have been used in combination, to monitor the dehydration process of fluconazole monohydrate (MH), this unveiling the dehydration mechanism at the molecular level. Experimentally, dehydration was observed to start at around 55 °C and complete around 100 °C, with metastable Pbca, Z’=1 polymorph (AH-C) as the sole product of dehydration (as determined by in-situ hot stage PXRD). Conformational and structural changes were identified as key in the initiation and progression of the dehydration process. Thermal expansion is most significant along the c-axis, with molecular dynamic (MD) simulations and experimental observations identifying that water migrates through the MH crystal lattice within the plane perpendicular to that direction. Water was found to migrate within the (001) plane along both the a and b-axis directions. The MD simulations revealed that water was not able to migrate within the lattice at room temperature. Migration at 70°C (342K) was plausible, but only after the hydroxyl group undergoes conformational change. The conformational change, around the hydroxyl group, is key to both the weakening of the fluconazole-water hydrogen bonding, found in the MH structure, and the promotion of the fluconazole-fluconazole hydrogen bonding, required for the formation of polymorph AH-C.

BACKGROUND Sarcopenic obesity (SO) is the coexistence of sarcopenia and obesity in an individual. The present study is designed to define the usefulness of skeletal muscle ultrasonography (US) in the definition of SO. METHODS Eighty-nine participants aged ≥65 whose body mass index (BMI, kg/m2 ) was ≥30 were consecutively enrolled in an outpatient clinic of geriatric medicine. All underwent comprehensive geriatric assessment. US measurements were obtained in 6 different muscles consisting of core and limb muscles. We defined SO as the presence of low muscle function (defined by a handgrip strength < 27 kg in males and

Background Hip fracture is both a cause and a consequence of sarcopenia. Older persons with sarcopenia have an increased risk of falling, and the prevalence of sarcopenia may be increased in those who suffer a hip fracture. The aim of this study was to explore potential biomarkers (neuromuscular and peripheral pro‐inflammatory and oxidative stress markers) that may be associated with sarcopenia in very old persons with hip fracture. Methods We recruited 150 consecutive patients ≥80 years old admitted to an orthogeriatric unit for an osteoporotic hip fracture. Muscle mass was assessed pre‐operatively using bioelectrical impedance analysis; Janssen's (J) and Masanés' (M) reference cut‐off points were used to define low muscle mass. Muscle strength was assessed with handgrip strength (Jamar's dynamometer). Sarcopenia was defined by having both low muscle mass and strength and using the European Working Group on Sarcopenia in Older People 2 definition of probable sarcopenia (low grip strength). Peripheral markers—pro‐inflammatory and oxidative stress parameters—were determined either in the plasma or in the erythrocyte fraction obtained from peripheral whole blood of every patient pre‐operatively. Results Mean age was 87.6 ± 4.9 years, and 78.7% were women. The prevalence of sarcopenia was 11.5% with Janssen's, 34.9% with Masanés' cut‐offs, and 93.3% with the European Working Group on Sarcopenia in Older People 2 definition of probable sarcopenia. Among the four pro‐inflammatory cytokines tested in plasma, only tumour necrosis factor‐α was different (lower) in sarcopenic than in non‐sarcopenic participants using both muscle mass cut‐offs (J 7.9 ± 6.2 vs. 8.3 ± 5.8, M 6.8 ± 4.7 vs. 9.1 ± 6.2). Erythrocyte glutathione system showed a non‐significant tendency to lower glutathione levels and glutathione/oxidized glutathione ratios in sarcopenic participants compared with non‐sarcopenic subjects. Catalase activity was also lower in sarcopenic participants (J 2904 ± 1429 vs. 3329 ± 1483, M 3037 ± 1430 vs. 3431 ± 1498). No significant differences were found between groups in chymotrypsin‐like activity of the 20S proteasome, superoxide dismutase, glutathione peroxidase and butyrylcholinesterase activity, C‐terminal agrin fragment, interferon‐γ, or interleukin‐1β. Conclusions The prevalence of sarcopenia in patients with hip fracture varies according to the definition and the muscle mass reference cut‐off points used. We did not find differences in most neuromuscular, pro‐inflammatory, or oxidative stress markers, except for lower peripheral tumour necrosis factor‐α levels and catalase activity in sarcopenic participants, which may be markers of an early inflammatory reaction that is hampered in sarcopenic patients.

Purpose of review To summarize the latest advances and caveats in defining sarcopenia and discuss the implications of the most recent worldwide initiatives which are trying to harmonize the definition. Recent findings The evolution over time of the definitions of sarcopenia is discussed, with a focus on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition and the Sarcopenia Definitions and Outcomes Consortium (SDOC) conference. The EWGSOP2 and the SDOC agree on the overall concept of sarcopenia, which involves both impaired function (low muscle strength) and structural damage (low muscle mass/quality). However, physical performance is considered as a diagnostic criterion (EWGSOP), a severity grading assessment (EWGSOP2) or an outcome (SDOC) pending on the definition used. Muscle strength has been recognized as the best predictor of health outcomes. Muscle mass alone, as part of the definition of cachexia, sarcopenia and malnutrition, is a nondefining parameter. Furthermore, there is a lack of precision in measurement techniques and variability of the cut-off points in defining it. Summary We discuss the relationship of sarcopenia with cachexia, malnutrition and frailty, and the areas that are hampering agreement. We summarize key scientific evidence, consider future study of this nutrition-related disease and raise concern about the need for a universal definition of sarcopenia.

Introduction: Opioid-Induced Constipation (OIC) is a common distressing symptom associated with cancer pain treatment. Consensus guidelines for management of OIC are limited and little is known about the decision making of Health Care Professionals (HCP) for the management of OIC. The aim of this study was to learn about the diagnostic and treatment criteria of OIC management in clinical practice in patients with cancer.

© 2021 Saiz-Ladera, Baliu-Piqué, Cimas, Manzano, García-Barberán, Camarero, Hinojal, Pandiella, Győrffy, Stewart, Cruz-Hernández, Pérez-Segura and Ocana., Targeting the immune system has emerged as an effective therapeutic strategy for the treatment of various tumor types, including Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-small-Cell Lung Cancer (NSCLC), and checkpoint inhibitors have shown to improve patient survival in these tumor types. Unfortunately, not all cancers respond to these agents, making it necessary to identify responsive tumors. Several biomarkers of response have been described and clinically tested. As of yet what seems to be clear is that a pre-activation state of the immune system is necessary for these agents to be efficient. In this study, using established transcriptomic signatures, we identified a group of gene combination associated with favorable outcome in HNSCC linked to a higher presence of immune effector cells. CD2, CD3D, CD3E, and CXCR6 combined gene expression is associated with improved outcome of HNSCC patients and an increase of infiltrating immune effector cells. This new signature also identifies a subset of cervical squamous cell carcinoma (CSCC) patients with favorable prognosis, who show an increased presence of immune effector cells in the tumor, which outcome shows similarities with the HP-positive HNSCC cohort of patients. In addition, CD2, CD3D, CD3E, and CXCR6 signature is able to predict the best favorable prognosis in terms of overall survival of CSSC patients. Of note, these findings were not reproduced in other squamous cell carcinomas like esophageal SCC or lung SCC. Prospective confirmatory studies should be employed to validate these findings., This work has been supported by Instituto de Salud Carlos III (PI16/01121 and PI19/00808), ACEPAIN; Diputación de Albacete, CIBERONC and CRIS Cancer Foundation (to AO). Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R), the Instituto de Salud Carlos III through the Spanish Cancer Centers Network Program (RD12/0036/0003) and CIBERONC, the scientific foundation of the AECC and the CRIS Foundation (to AP). The work carried out in our laboratories receive support from the European Community through the regional development funding program (FEDER).

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8+ T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8+ T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8+ T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors.

Background and Objectives To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). Methods Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. Results Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R-2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. Discussion Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS., This work was supported by the European Regional Development Fund and the Spanish Ministry of Science, Innovation and Universities (grant: RTI2018-096951-A-I00) and the Ministry of Economy and Competitiveness (grant: RYC-2015-18467).

Purpose: This work presents a case of syphilitic outer retinopathy with findings similar to those of acute zonal occult outer retinopathy (AZOOR). We also discuss the clinical characteristics, treatment, and prognosis of this entity. Methods: A case report and systematic literature review are presented. Results: A 56-year-old woman presented with acute vision loss, localized photopsia, a central scotoma, and retinal findings that were all consistent with AZOOR. A further workup led to a diagnosis of syphilis. Oral prednisone and intravenous penicillin resulted in the resolution of the posterior uveitis and the restoration of visual acuity. However, the central scotoma remained at the 3-year follow-up visit. Conclusions: Syphilitic outer retinopathy is a distinct entity characterized by the disruption of the ellipsoid zone visible on optical coherence tomography and a corresponding increase in fundus hyperautofluorescence in the affected areas. Although some patients may present with a demarcation line, as is seen with AZOOR, the fundus is oftentimes unremarkable or may show only subtle retinal pigment epithelium changes. Uveitis resolution and visual acuity restoration may be expected following treatment; however, visual field disturbances may persist.

Nanotechnology is a promising tool for the treatment of cancer. In the past decades, major steps have been made to bring nanotechnology into the clinic in the form of nanoparticle-based drug delivery systems. The great hope of drug delivery systems is to reduce the side effects of chemotherapeutics while simultaneously increasing the efficiency of the therapy. An increased treatment efficiency would greatly benefit the quality of life as well as the life expectancy of cancer patients. However, besides its many advantages, nanomedicines have to face several challenges and hurdles before they can be used for the effective treatment of tumors. Here, we give an overview of the hallmarks of cancer, especially colorectal cancer, and discuss biological barriers as well as how drug delivery systems can be utilized for the effective treatment of tumors and metastases.

Introduction Immunotherapy represents one of the fundamental points on the oncological treatments. The increasingly frequent use of these treatments has allowed us to observe various side effects in up to 10 to 20% of patients and endocrine side effects are one of the most commonly described. We report a case of diabetic ketoacidosis in a 46-year-old male patient as debut of type-1 diabetes mellitus secondary to treatment with nivolumab. Case Report The patient who went to the emergency department due to abdominal pain associated with vomiting 48 hours previously. Diagnosed 4 years ago of clear cell renal carcinoma stage IV, due to pulmonary metastatic involvement, the patient was under treatment with nivolumab. Urgent blood and urine tests were performed in the urgency evaluation; the patient was diagnosis of severe diabetic ketoacidosis. Pancreatic endocrine complications are observed in 0.5 to 5% of the patients with immunotherapy. Among the adverse effects described are alterations in baseline fasting glycaemia and the possible development of type-1 diabetes. These molecules increase the activity of T-cells, amplify the cellular immune activity with the consequent increased immune response, which can lead to a destruction of the pancreatic β-cells. Strict endocrine control is necessary during immunotherapy treatment; however, there are no clear indications for the monitoring of pancreatic reserve levels or glycemic control. For these reasons, we propose the need for closer and regular monitoring of C-peptide and HbA1c (glycosylated hemoglobin) to prevent the development of the diabetes and their complications.

Recent definitions of malnutrition include low muscle mass within its diagnostic criteria. In fact, malnutrition is one of the main risk factors of skeletal muscle loss contributing to the onset of sarcopenia. However, differences in the screening and diagnosis of skeletal muscle loss, especially as a result of malnutrition in clinical and community settings, still occur mainly as techniques and thresholds used vary in clinical practice. The objectives of this position paper are firstly to emphasize the link between skeletal muscle loss and malnutrition-related conditions and secondly to raise awareness for the timely identification of loss of skeletal muscle mass and function in high risk populations. Thirdly to recognize the need to implement appropriate nutritional strategies for prevention and treatment of skeletal muscle loss and malnutrition across the healthcare continuum. Malnutrition needs to be addressed clinically as a muscle-related disorder and clinicians should integrate nutritional assessment with muscle mass measurements for optimal evaluation of these two interrelated entities to tailor interventions appropriately. The design of monitoring/evaluation and discharge plans need to include multimodal interventions with nutrition and physical exercise that are key to preserve patient's muscle mass and function in clinical and community settings.

The term sarcopenia was introduced in 1988. The original definition was a “muscle loss” of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

Background Adverse drug reactions (ADRs) are common and have serious repercussions for older-adults. This descriptive-analysis elucidates clinical presentations, severity and responsible drugs of incident ADRs in the SENATOR (Software ENgine for the Assessment & optimization of drug and non-drug Therapy in Older peRsons) phase I feasibility study. Methods SENATOR-phase-I was a European multicentre-prospective-observational study. Participants were ≥ 65 years, experiencing acute-hospitalisation and on pharmacological treatment for ≥ 3 conditions. Adverse events (AEs) were identified by trigger list at recruitment, day-14/discharge and classified as ADRs when association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre ADR causality criteria. Results Of 644 participants recruited, 382 (59.1%) experienced 732 AEs, 363 AEs (49.6%) being incident. 139 participants (21.6%) experienced 177 (48.8%) ADRs. Full drug details were recorded in 156 patients (88%). Cardiovascular-system drugs accounted for one-third of ADRs (55, 35.3%). Five drug classes caused three-quarters of ADRs (135, 76.3%); diuretics 28.2% (furosemide 24.4%), opioid analgesics 16.7%, anti-bacterials for systemic use 14.1%, anti-thrombotic agents 10.3%, and drugs used in diabetes 7%. 68 patients (10.6%) experienced 81 (45.8%) clinically significant moderate-severe ADRs. Significant serum electrolyte disturbance (32, 18.1%), acute kidney injury [AKI] (22, 12.4%), unspecified adverse event (UAE; 21, 11.9%), dyspepsia/nausea/vomiting (20, 11.3%), new-onset major constipation (19, 10.7%) were the most common presentations of ADRs, accounting for 114, (64.4%) of all ADRs. In moderate-severe ADRs; AKI (12, 14.8%), acute bleeding (11, 13.6%), new-onset major constipation (11, 13.6%), UAE (11, 13.6%), significant serum electrolyte disturbance (10, 12.4%) were the most common presentations. Conclusion This analysis highlights that; 1-in-5 older adults will experience an incident ADR during acute hospitalisation. 1-in-10 patients experience moderate-severe incident ADRs. 3-of-4 ADRs were caused by 5 drug classes (diuretics, opioids, anti-bacterials, anti-thrombotics and anti-diabetic agents). This study allows for identification of potentially high risk medications which could be targeted for future ADR prevention.

Introduction Malnutrition is common among older people living in nursing homes. Poor nutritional status is associated with functional loss and with worse health. Oral nutritional supplementation (ONS) can be an effective means to counteract weight loss, improve nutritional status and reduce complications in malnourished older people living in nursing homes. The main objective of this study was to assess whether ONS over 12 weeks improved the nutritional status and physical function of malnourished older people living in nursing homes. Methods This was a multi-center, prospective, observational study carried out in 53 nursing homes in Spain. Participants were aged 65 or over. They were prescribed a high-calorie, high-protein ONS to treat well documented malnutrition. Subjects who received enteral nutrition, had special nutritional requirements, or receiving end-of-life care were excluded. Anthropometric data were recorded (weight, height and BMI) as well as scores on nutritional and functional scales (MNA-SF, Barthel index, SPPB, grip strength and Functional Ambulation Categories, FAC) at the beginning of the study and after 12 weeks. Cognitive status, comorbidities and depressive symptoms were also assessed. Frailty status was assessed using the FRAIL scale. Results 320 participants were included, of whom 253 completed the study (mean age 84.2 ± 7.1 years). Baseline BMI was 20.2 ± 2.8. A high prevalence of functional impairment (Barthel Index median 45, range 15–75; median SPPB 4, range 1–6) and cognitive impairment (MMSE median 12, 7–20) was found. Discussion This study identified a population with malnutrition and a high degree of physical and mental disability that mirrors the typical population of many nursing homes. Analysis of the results of this study will help to determine the factors associated with malnutrition and the effect of nutritional intervention in practice.

Frailty is a multidimensional condition common in older adults, where reduced resiliency leads to adverse outcomes. It has strong links with malnutrition and sarcopenia, mostly through muscle health. This review explores the links between nutrition and frailty from different perspectives.Studies linking malnutrition and frailty show that most malnourished persons are frail, and malnutrition risk is increased in frail people. Energy and protein intake and some micronutrients are linked to frailty. Research on the role of microbiota and specific amino acids is increasing. Recent literature on the prevention of frailty with nutrition confirms that an appropriate intake of proteins, vitamin D and other nutrients is needed, but this information is still not in the public domain. Interventions to reverse frailty and sarcopenia should include exercise and nutrition interventions, usually with a multidomain approach including other elements.Public health recommendations to eat an optimal diet with the right amount of energy and proteins should be moved to the public domain. Whenever frailty is present, nutrition has a role in reverting it and avoiding adverse outcomes, but high-quality research is still needed in this area.

Multiple medication and inappropriate drug prescription are prevalent and challenging problems in older patients in end-of-life situations, and increases both preventable adverse events and health care costs. Recent literature recommends de-prescribing some drugs in patients with short life expectancy, when the aim of drug treatments is not prevention or cure, but symptom control. Recently, a list of explicit criteria (STOPP-Frail) intended to guide prescribing physicians in decision making on the use of drugs in older patients with terminal conditions. This article presents a Spanish version of such criteria, which have been named STOPP-Pal to avoid confusion with the current concept of frailty.

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

This systematic review aimed to determine if non-pharmacological interventions can impact upon older stroke survivors quality of life. From 28 trials we identified limited evidence supporting a beneficial impact upon quality of life from additional physiotherapy and occupational therapy. Very limited evidence supported the use of a wide array of other non-pharmacological therapies. Current evidence is limited by low study quality and small sample sizes and more trials specifically involving older stroke survivors are required. The efficacy of non-pharmacological stroke rehabilitation approaches for older stroke survivors is largely unknown, particularly in relation to psychosocial outcomes such as quality of life. This systematic review examined the evidence for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project conducted under an European Union funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [ http://www.senator-project.eu ]. Thirteen experts in geriatric medicine, as part of a Delphi panel, agreed quality of life to be a critical outcome of stroke rehabilitation. A comprehensive search strategy was developed and databases were searched for eligible systematic reviews from which trials meeting our criteria were identified. Eligible papers were then double reviewed. Due to heterogeneity, narrative analysis was performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence. We identified 28 trials, spanning ten types of intervention. Limited evidence supports the use of additional occupational therapy and physiotherapy, with very limited evidence supporting our recommendation to explore caregiver training, constraint-induced movement therapy, device-assisted physiotherapy, and self-management education further. Limited evidence suggests a range of non-pharmacological interventions may improve the quality of life of older stroke survivors. However, evidence is limited by low study quality and the small number of studies targeting older stroke survivors. We recommend future studies explore such interventions exclusively in older adult populations and improve methodological and outcome reporting.

Preserving muscle is not only crucial for maintaining proper physical movement, but also for its many metabolic and homeostatic roles. Low muscle mass has been shown to adversely affect health outcomes in a variety of disease states (eg, chronic obstructive pulmonary disease, cancer, cardiovascular disease) and leads to an increased risk for readmission and mortality in hospitalized patients. Low muscle mass is now included in the most recent diagnostic criteria for malnutrition. Current management strategies for malnutrition may not prioritize the maintenance and restoration of muscle mass. This likely reflects the challenge of identifying and measuring this body composition compartment in clinical practice and the lack of awareness by health care professionals of the importance that muscle plays in patient health outcomes. As such, we provide a review of current approaches and make recommendations for managing low muscle mass and preventing muscle loss in clinical practice. Recommendations to assist the clinician in the optimal management of patients at risk of low muscle mass include the following: (1) place muscle mass at the core of nutritional assessment and management strategies; (2) identify and assess low muscle mass; (3) develop a management pathway for patients at risk of low muscle mass; (4) optimize nutrition to focus on muscle mass gain versus weight gain alone; and (5) promote exercise and/or rehabilitation therapy to help maintain and build muscle mass. The need to raise awareness of the importance of screening and managing 'at risk' patients so it becomes routine is imperative for change to occur. Health systems need to drive clinicians to treat patients with this focused approach, and the economic benefits need to be communicated to payers. Lastly, further focused research in the area of managing patients with low muscle mass is warranted.

Kaposi sarcoma is a vascular sarcoma with 4 clinical variants: classic Kaposi sarcoma, which mainly affect the extremities of elderly patients and follows a chronic, generally indolent course; African Kaposi sarcoma; immunosuppression-associated Kaposi sarcoma; and AIDS-associated Kaposi sarcoma. Type8 human herpesvirus is the etiologic agent in all 4variants. Cutaneous angiosarcoma is a cutaneous neoplasm with a very poor prognosis. It carries a high probability of local relapse and has a 10% to 15% survival rate at 5years. There are 3 main variants of cutaneous angiosarcoma: idiopathic angiosarcoma of the face and scalp; Stewart-Treves syndrome; and postradiation angiosarcoma. The only potentially curative treatment is surgery with or without radiotherapy. However, its indistinct borders and multicentric nature mean that treatment is often palliative with chemotherapy, radiotherapy, or both.

Publisher's version (útgefin grein), Background:The ongoing “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment stra-tegies (SPRINTT)” randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention inthe prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describethe procedures followed for PF&S case finding and screening of candidate participants for the SPRINTT RCT. Wealso illustrate the main demographic and clinical characteristics of eligible screenees.Methods:The identification of PF&S was based on the co-occurrence of three defining elements: (1) reducedphysical performance (defined as a score on the Short Physical Performance Battery between 3 and 9); (2) lowmuscle mass according to the criteria released by the Foundation for the National Institutes of Health; and (3)absence of mobility disability (defined as ability to complete the 400-m walk test in 15 min). SPRINTT wasadvertised through a variety of means. Site-specific case finding strategies were developed to accommodate thevariability across centers in catchment area characteristics and access to the target population. A quick “parti-cipant profiling” questionnaire was devised to facilitate PF&S case finding.Results:During approximately 22 months, 12,358 prescreening interviews were completed in 17 SPRINTT sitesresulting in 6710 clinic screening visits. Eventually, 1566 candidates were found to be eligible for participatingin the SPRINTT RCT. Eligible screenees showed substantial physical function impairment and comorbidityburden. In most centers, project advertisement through mass media was the most rewarding case findingstrategy.Conclusion:PF&S case finding in the community is a challenging, but feasible task. Although largely autonomousin daily life activities, older adults with PF&S suffer from significant functional impairment and comorbidity.This subset of the older population is therefore at high risk for disability and other negative health-relatedevents. Key strategies to consider for successfully intercepting at-risk older adults should focus on mass com-munication methods., The present work was funded by a grant from the InnovativeMedicines Initiative - Joint Undertaking (IMI-JU 115621). The workwas also partly supported by the nonprofit research foundation “CentroStudi Achille e Linda Lorenzon” and by intramural research grants fromthe Università Cattolica del Sacro Cuore (D3.2 2013 and D3.2 2015).The authors thank all the participants and the staff involved in thetrial for the enthusiastic participation and dedication.

Key Summary Points Aim The prevalence of MCI is underestimated owing to underdiagnosis, resulting in a lack of timely intervention and undetected disease progression. This article aims to assess the effect of ketogenic supplements/diets on brain metabolism, including evidence supporting the efficcy of ketones as an efficient fuel for the brain. Findings The 6-month randomized controlled BENEFIC trial showed that consumption of a ketogenic MCT drink improved cognitive performance in individuals with MCI compared with placebo. Message There is evidence to support the efficacy of nutritional interventions such as ketogenic supplements/diets, which offer ketones as an alternative energy source for brain cells., Background Mild cognitive impairment (MCI) is characterized by a decline in cognition and mainly affects older individuals above the age of 60. The global incidence of MCI varies, but it is often underdiagnosed and untreated. There is a distinct lack of approved pharmacologic options to treat MCI. There is, however, evidence to support the efficacy of nutritional interventions, such as ketogenic supplements/diets, which offer ketones as an alternative energy source to brain cells. This article explores the effect of ketones on metabolic activity in the brain and the mechanisms by which ketogenic medium-chain triglycerides (kMCTs) induce ketosis in patients with MCI. Key takeaways This article reviews the effect of ketogenic supplements/diets on brain metabolism, including evidence supporting the efficacy of ketones as an efficient fuel for the brain. It discusses the use of oral nutritional ketogenic supplements, with particular reference to the 6-month randomized controlled BENEFIC trial, which showed that consumption of a kMCT drink, BrainXpert Energy Complex, improved cognitive performance in individuals with MCI compared with placebo. Conclusion While there is a need for more long-term studies, results from the BENEFIC trial revealed the benefits of a brain-specific ketogenic supplement, as a nutritional intervention, on cognitive performance in individuals with MCI.

Background and Purpose Inflammation associated with the tumour microenvironment (TME) is critical for cancer development, and immunotherapeutic strategies modulating the immune response in cancer have been crucial. In this study, a methotrexate-loaded (MTX) poly(lactic-co-glycolic acid)-based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with an PD-L1 antibody to investigate anti-cancer and immunomodulatory effects in breast cancer TME.Experimental Approach Naked or HA-coated PeiPLGA-MTX nanoparticles (NPs) were assessed on 4T1 breast cancer cells grown in culture and in a mouse model of orthotopic tumour growth. Tumours were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and cell migration were analysed in vitro in 4T1 cells. Polarization of murine macrophages (RAW cells) was also carried out.Key Results Naked or HA-coated PeiPLGA-MTX NPs used alone or combined with PD-L1 antibody modified the tumourigenic course by TME immunomodulation, leading to reduction of primary tumour size and metastases. STAT3 and NF-kappa B were the major genes downregulated by NPs. In tumor-associated macrophages (TAM) such regulation switched M2 phenotype (CD163) towards M1 (CD68) and reduced levels of IL-10, TGF-beta and CCL22. Moreover, malignant cells showed overexpression of FADD, APAF-1, caspase-3 and E-cadherin, and decreased expression of Bcl-2, MDR-1, survivin, vimentin, CXCR4 and PD-L1 after treatment with NPs.Conclusion and Implications NPs-mediated STAT3/NF-kappa B signalling axis suppression disrupted crosstalk between immune and malignant cells, reducing immunosuppression and critical pro-tumour events. These findings provide a promising therapeutic approach capable of guiding the immune TME to suppress the development of breast cancer.

Producción Científica, Polymer-based tri-layered (bone, intermediate and top layers) scaffolds used for the restoration of articular cartilage were prepared and characterized in this study to emulate the concentration gradient of cartilage. The scaffolds were physically or chemically crosslinked. In order to obtain adequate scaffolds for the intended application, the impact of the type of calcium phosphate used in the bone layer, the polymer used in the intermediate layer and the interlayer crosslinking process were analyzed. The correlation among SEM micrographs, physical-chemical characterization, swelling behavior, rheological measurements and cell studies were examined. Storage moduli at 1 Hz were 0.3–1.7 kPa for physically crosslinked scaffolds, and 4–5 kPa (EDC/NHS system) and 15–20 kPa (glutaraldehyde) for chemically crosslinked scaffolds. Intrinsic viscoelasticity and poroelasticity were considered in discussing the physical mechanism dominating in different time/frequency scales. Cell evaluation showed that all samples are available as alternatives to repair and/or substitute cartilage in articular osteoarthritis., The European Union through the Erasmus MUNDUS LINDO post-doctoral fellowship,(project code ML14PD1157) and Erasmus PLUS doctoral fellowship, (project code 2015-1-NL01-KA 107-008639), European Union’s Horizon 2020 research and innovation program. grant agreement - H2020- MSCA-RISE (644373—PRISAR), H2020-MSCA-RISE (777682—CANCER), H2020-WIDESPREAD-05- 2017-Twinning (807281—ACORN), H2020-WIDESPREAD-2018-03 (852985—SIMICA), H2020-SCA RISE-2016 (734684—CHARMED) and MSCA-ITN-2015-ETN (675743—ISPIC), 861190 (PAVE), 857894 (CAST), 859908 (NOVA-MRI); 872860 (PRISAR2), VIDI grant (project number 723.012.110)

Interactions among physiological pathways associated with osteoporosis and sarcopenia are thought to contribute to the onset of frailty. The International Conference on Frailty and Sarcopenia Research Task Force thus met in March 2020 to explore how emerging interventions to manage fracture and osteoporosis in older adults may reduce frailty, disability, morbidity, and mortality in the older population. Both pharmacological and non-pharmacological interventions (including nutritional intervention, exercise, and other lifestyle changes) were discussed, including nutritional intervention, exercise, and other lifestyle changes. Pharmacological treatments for osteoporosis include bone-forming and antiresorptive agents, which may optimally be used in sequential or combination regimens. Since similar mechanisms related to resorption underlie physiological changes in muscle and bone, these interventions may provide benefits beyond treating osteoporosis. Clinical trials to test these interventions, however, often exclude frail older persons because of comorbidities (such as mobility disability and cognitive impairment) or polypharmacy. The Task Force recommended that future clinical trials use harmonized protocols, including harmonized inclusion criteria and similar outcome measures; and that they test a range of multidomain therapies. They further advocated more high-quality research to develop interventions specifically for people who are frail and old. The ICOPE program recommended by WHO appears to be highly recommended to frail older adults with osteoporosis.

Introduction Sarcopenia is defined by a loss of muscle mass and function associated with mortality, decreased physical performance, falls, and disability. Since chronic inflammation and decreased physical activity are risk factors for developing sarcopenia, it is critical to assess the role of sarcopenia in immune-mediated rheumatic diseases (IMRDs). Moreover, nutritional interventions are emerging as key modifiable and affordable options to improve physical performance in sarcopenia. Objective The aim of this review is to critically summarize current information on the evidence linking nutritional interventions and sarcopenia in IMRDs. Methods The search and selection of articles was performed in Medline, Dimensions.ai, Google Scholar, Cochrane Library, Epistemonikos, and Trip Database. The results were clustered into three areas: sarcopenia and IMRDs, sarcopenia and biological disease-modifying antirheumatic drugs (bDMARDs), and nutritional interventions for sarcopenia. Findings Several cross-sectional studies have shown a higher prevalence of sarcopenia in IMRDs, such as rheumatoid arthritis. Although not fully established, evidence linking sarcopenia and other IMRDs (ankylosing spondylitis and systemic sclerosis) has been also described. For secondary sarcopenia prevention and treatment, bDMARDs’ administration proved efficacy in patients with rheumatoid arthritis. Furthermore, there is growing evidence linking nutrition to the prevention and treatment of sarcopenia. Evidence linking unfavourable results in nutritional risk assessment, insufficient intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acids and sarcopenia have been reported. Conclusion Given that sarcopenia and IMRDs have strong links, further research is needed to improve patient care.

© 2021 by the authors., The dopaminergic system can adapt to the different physiological or pathological situations to which the kidneys are subjected throughout life, maintaining homeostasis of natriuresis, extracellular volume, and blood pressure levels. The role of renal dopamine receptor dysfunction is clearly established in the pathogenesis of essential hypertension. Its associations with other pathological states such as insulin resistance and redox balance have also been associated with dysfunction of the dopaminergic system. The different dopamine receptors (D1–D5) show a protective effect against hypertension and kidney disorders. It is essential to take into account the various interactions of the dopaminergic system with other elements, such as adrenergic receptors. The approach to therapeutic strategies for essential hypertension must go through the blocking of those elements that lead to renal vasoconstriction or the restoration of the normal functioning of dopamine receptors. D1-like receptors are fundamental in this role, and new therapeutic efforts should be directed to the restoration of their functioning in many patients. More studies will be needed to allow the development of drugs that can be targeted to renal dopamine receptors in the treatment of hypertension.

Soft-tissue sarcomas constitute an uncommon and heterogeneous group of tumors of mesenchymal origin. Diagnosis, treatment, and management should be performed by an expert multidisciplinary team. MRI/CT of the primary tumor and biopsy is mandatory before any treatment. Wide surgical resection with tumor-free tissue margin is the mainstay for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not suitable for re-excision. Perioperative chemotherapy should be discussed for high-risk sarcomas of the extremities and trunk-wall. In the case of oligometastatic disease, patients should be considered for local therapies. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. Other drugs have shown activity in second-line therapy and in specific histological subtypes but options are limited and thus, a clinical trial should always be discussed.

Purpose: In 2018, the SARCUS working group published a first article on the standardization of the use of ultrasound to assess muscle. Recommendations were made for patient positioning, system settings and components to be measured. Also, shortcomings in knowledge were mentioned. An important issue that still required standardization was the definition of anatomical landmarks for many muscles. Methods: A systematic search was performed in Medline, SCOPUS and Web of Sciences looking for all articles describing the use of ultrasound in the assessment of muscle not described in the first recommendations, published from 01/01/2018 until 31/01/2020. All relevant terms used for older people, ultrasound and muscles were used. Results: For 39 muscles, different approaches for ultrasound assessment were found that likely impact the values measured. Standardized anatomical landmarks and measuring points were proposed for all muscles/muscle groups. Besides the five already known muscle parameters (muscle thickness, cross-section area, pennation angle, fascicle length and echo-intensity), four new parameters are discussed (muscle volume, stiffness, contraction potential and microcirculation). The former SARCUS article recommendations are updated with this new information that includes new muscle groups. Conclusions: The emerging field of ultrasound assessment of muscle mass only highlights the need for a standardization of measurement technique. In this article, guidelines are updated and broadened to provide standardization instructions for a large number of muscles., SCOPUS: re.j, info:eu-repo/semantics/published

Background and Aims. Gastric cancer is the 5th leading cause of cancer mortality worldwide and the leading infection-associated cancer. Helicobacter pylori is the most common chronic bacterial infection in humans and the major predisposing factor for the development of gastric intestinal metaplasia (GIM), the principal preneoplastic lesion in the gastric carcinogenesis pathway. GIM surveillance is now recommended for individuals among high-risk subgroups by three major gastroenterology societies in Europe, England, and U.S. Our objective was to provide the initial epidemiologic data for GIM among Hispanics in Puerto Rico. Methods. Using a cross-sectional study design, we analyzed an extensive pathology database ( n = 43,993 ) that captured approximately 50% of all endoscopy biopsies taken during 2012-2014 at academic, public, and private sectors in Puerto Rico. Prevalence estimates of GIM, GIM subgroups, and H. pylori status were estimated using logistic regression models. Results. A total of 4,707 GIM cases were identified during the study period for a prevalence rate of 10.7%. H. pylori was detected in 26.9% (95% CI: 25.7-28.2) of the GIM cases. The majority of the pathology reports lacked information regarding the high-risk subtypes (99.6%) and extension (71.2%). Conclusions. The prevalence of GIM among Hispanics living in Puerto Rico may be higher than in U.S. mainland non-Hispanic populations. The prevalence of H. pylori detected in our study population was comparable to the rates reported in the mainland U.S. Standardization of the endoscopy biopsy protocol and pathology reporting is needed to characterize and risk stratify GIM surveillance programs in Puerto Rico.

A 73-year-old male with a history of chronic obstructive pulmonary disease and stage IV lung adenocarcinoma, being treated with the PD-1 inhibitor nivolumab, presented to the Emergency Room with a two-day history of coffee ground emesis and melena. On examination, he was tachycardic (130 per minute) and hypotensive (95/55 mmHg). Laboratory studies revealed anemia (6.9 g/dl), leukocytosis and hyper-lactatemia (lactate 6.3 mmol/l). Esophagogastroduodenoscopy was performed which showed diffuse circumferential blackish, necrotic-appearing mucosa of the first third of the esophagus. These findings were consistent with a diagnosis of acute esophageal necrosis (AEN). A biopsy of the esophageal mucosa demonstrated fragments of necrotic tissue with predominant lymphocyte infiltration. He was managed with a strict restriction of oral intake, total parenteral nutrition, double-dose proton pump inhibitors and broad-spectrum antibiotics (piperacillin/tazobactam). Despite the measures adopted, the patient presented a progressive clinical deterioration and died of multiple organ failure 12 days after admission.

International audience; The aging population faces two conditions that threaten healthy aging: high fat mass (obesity) and low muscle mass and function (sarcopenia). The combination of both—referred to as sarcopenic obesity—synergistically increases the risk of adverse health outcomes. The two conditions often co-occur because they reinforce each other and share common etiologies, including poor nutrition and inactivity. All aging people are at risk of gaining weight and losing muscle mass and could benefit from improvements in physical activity, exercise and dietary intake. one specific window of opportunity is during the transient time of retirement, as older adults already need to restructure their daily activities. It is key to change lifestyle behavior in a sustainable manner, providing scientifically proven, personalized, and acceptable principles that can be integrated in daily life. Health technologies (e.g., applications) can provide promising tools to deliver personalized and appealing lifestyle interventions to a large group of people while keeping health care costs low. Several studies show that health technologies have a strong positive effect on physical activity, exercise and dietary intake. Specifically, health technology is increasingly applied to older people, although strong evidence for long term effects in changing lifestyle behavior is generally lacking. Concluding, technology could play an important role in the highly warranted prevention of sarcopenic obesity in older adults. Although health technology seems to be a promising tool to stimulate changes in physical activity, exercise and dietary intake, studies on long lasting effects and specifically targeted on older people around the time of retirement are warranted.

One of the challenges of nanotechnology is to improve the efficacy of treatments for diseases, in order to reduce morbidity and mortality rates. Following this line of study, we made a nanoparticle formulation with a small size, uniform surfaces, and a satisfactory encapsulation coefficient as a target for colorectal cancer cells. The results of binding and uptake prove that using the target system with folic acid works: Using this system, cytotoxicity and cell death are increased when compared to using free oxaliplatin. The data show that the system maximized the efficiency of oxaliplatin in modulating tumor progression, increasing apoptosis and decreasing resistance to the drug. Thus, for the first time, our findings suggest that PLGA-PEG-FA increases the antitumor effectiveness of oxaliplatin by functioning as a facilitator of drug delivery in colorectal cancer.